There is a constant need for methods for the safe and effective administration of physiologically active agents, such as anti-alopecia agents. For many medications it is important that the administration regime is as simple and non-invasive as possible in order to maintain a high level of compliance by the patient.
Oral administration is one particular regime that is commonly used because it is a relatively simple to follow. However, the oral administration route is also complicated because of complications associated with gastrointestinal irritation and with drug metabolism in the liver. These complications may result in side effects, including mood disturbance (Altomare et al., 2002, J Dermatol. 29(10):665-9), unilateral gynecomastia (Ferrando et al., 2002, Arch Dermatol. 138(4):543-4), decreased libido, erectile dysfunction and ejaculation disorder as reported for the oral administration of finasteride (McClellan et al., 1999, Drugs 57(1):111-26).
Administration of physiologically active agents through the skin (‘topical drug delivery’) has received increased attention because it not only provides a relatively simple dosage regime but it also provides a relatively slow and controlled route for release of a physiologically active agent into the local tissue. However, topical drug delivery is complicated by the fact that the skin behaves as a natural barrier and therefore transport of agents through the skin is a complex mechanism.
Structurally, the skin consists of two principle parts, a relatively thin outermost layer (the ‘epidermis’) and a thicker inner region (the ‘dermis’). The outermost layer of the epidermis (the ‘stratum corneum’) consists of flattened dead cells which are filled with keratin. The regions between the flattened dead cells of the stratum corneum are filled with lipids which form lamellar phases that are responsible for the natural barrier properties of the skin.
For effective local delivery of a physiologically active agent applied to the surface of the skin (‘topical application’), the agent must be partitioned firstly from the vehicle into the stratum corneum, it must typically then be diffused within the stratum corneum before being partitioned from the stratum corneum to the local tissues including the viable epidermis, dermis, subcutis and appendageal.
To overcome some of the problems with topical delivery that are associated with transport across the dermal layers (‘percutaneous absorption’), physiologically active agents are commonly formulated with incorporation of one or more dermal penetration enhancers which are often lipophilic chemicals that readily partition into the stratum corneum whereupon they exert their effects on improving the transport of drugs across the skin barrier (Finnin et al., 1999, J.Pharm Sci., 88(10), 755-758).
There is a need for improved compositions for topical delivery of anti-alopecia agents.